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. 1989 Aug;30(8):1116–1122. doi: 10.1136/gut.30.8.1116

Randomised controlled trial of interferon alfa 2A (rbe) (Roferon-A) for the treatment of chronic hepatitis B virus (HBV) infection: factors that influence response.

M G Brook 1, J A McDonald 1, P Karayiannis 1, L Caruso 1, G Forster 1, J R Harris 1, H C Thomas 1
PMCID: PMC1434168  PMID: 2670693

Abstract

In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p less than 0.02) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/m2 and 2.5 MU/m2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p less than 0.005) lost HBeAg and 17% (5/29) lost hepatitis B surface antigen (HBsAg). The response rate among these anti-HIV negative patients receiving at least three months therapy was 46% and 19% respectively. Low pretreatment HBV-DNA and absence of anti-HIV were the only significant independent variables predicting response to therapy (p less than 0.03 and p less than 0.05 respectively). In six patients, neutralising antibodies to alpha interferon were detected during therapy, the majority being non-responders.

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Selected References

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  1. Abb J., Zachoval R., Eisenburg J., Pape G. R., Zachoval V., Deinhardt F. Production of interferon alpha and interferon gamma by peripheral blood leukocytes from patients with chronic hepatitis B virus infection. J Med Virol. 1985 Jun;16(2):171–176. doi: 10.1002/jmv.1890160209. [DOI] [PubMed] [Google Scholar]
  2. Alexander G. J., Brahm J., Fagan E. A., Smith H. M., Daniels H. M., Eddleston A. L., Williams R. Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet. 1987 Jul 11;2(8550):66–69. doi: 10.1016/s0140-6736(87)92735-8. [DOI] [PubMed] [Google Scholar]
  3. Biagiotti R., Giudizi M. G., Almerigogna F., Mazzetti M., Alessi A., Del Prete G. F., Rafanelli D., Fiorilli M., Morfini M., Romagnani S. Abnormalities of in vitro immunoglobulin production in apparently healthy haemophiliacs: relationship with alterations of T cell subsets and with HTLV-III seropositivity. Clin Exp Immunol. 1986 Feb;63(2):354–358. [PMC free article] [PubMed] [Google Scholar]
  4. Carne C. A., Weller I. V., Sutherland S., Cheingsong-Popov R., Ferns R. B., Williams P., Mindel A., Tedder R., Adler M. W. Rising prevalence of human T-lymphotropic virus type III (HTLV-III) infection in homosexual men in London. Lancet. 1985 Jun 1;1(8440):1261–1262. doi: 10.1016/s0140-6736(85)92324-4. [DOI] [PubMed] [Google Scholar]
  5. Dooley J. S., Davis G. L., Peters M., Waggoner J. G., Goodman Z., Hoofnagle J. H. Pilot study of recombinant human alpha-interferon for chronic type B hepatitis. Gastroenterology. 1986 Jan;90(1):150–157. doi: 10.1016/0016-5085(86)90087-9. [DOI] [PubMed] [Google Scholar]
  6. Douglas J. M., Jr, Rogers M., Judson F. N. The effect of asymptomatic infection with HTLV-III on the response of anogenital warts to intralesional treatment with recombinant alpha 2 interferon. J Infect Dis. 1986 Aug;154(2):331–334. doi: 10.1093/infdis/154.2.331. [DOI] [PubMed] [Google Scholar]
  7. Ellis W. R., Murray-Lyon I. M., Coleman J. C., Evans B. A., Fluker J. L., Bull J., Keeling P. W., Simmons P. D., Banatvala J. E., Willcox J. R. Liver disease among homosexual males. Lancet. 1979 Apr 28;1(8122):903–905. doi: 10.1016/s0140-6736(79)91376-x. [DOI] [PubMed] [Google Scholar]
  8. Goodall A. H., Meek F. L., Waters J. A., Miescher G. C., Janossy G., Thomas H. C. A rapid one-step radiometric assay for hepatitis B surface antigen utilizing monoclonal antibodies. J Immunol Methods. 1982 Jul 30;52(2):167–174. doi: 10.1016/0022-1759(82)90042-4. [DOI] [PubMed] [Google Scholar]
  9. Hoofnagle J. H., Dusheiko G. M., Seeff L. B., Jones E. A., Waggoner J. G., Bales Z. B. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med. 1981 Jun;94(6):744–748. doi: 10.7326/0003-4819-94-6-744. [DOI] [PubMed] [Google Scholar]
  10. Ikeda T., Lever A. M., Thomas H. C. Evidence for a deficiency of interferon production in patients with chronic hepatitis B virus infection acquired in adult life. Hepatology. 1986 Sep-Oct;6(5):962–965. doi: 10.1002/hep.1840060525. [DOI] [PubMed] [Google Scholar]
  11. Karayiannis P., Fowler M. J., Lok A. S., Greenfield C., Monjardino J., Thomas H. C. Detection of serum HBV-DNA by molecular hybridisation. Correlation with HBeAg/anti-HBe status, racial origin, liver histology and hepatocellular carcinoma. J Hepatol. 1985;1(2):99–106. doi: 10.1016/s0168-8278(85)80759-5. [DOI] [PubMed] [Google Scholar]
  12. Krohn K., Ranki A., Antonen J., Valle S. L., Suni J., Vaheri A., Saxinger C., Gallo R. C. Immune functions in homosexual men with antibodies to HTLV-III in Finland. Clin Exp Immunol. 1985 Apr;60(1):17–24. [PMC free article] [PubMed] [Google Scholar]
  13. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  14. Liaw Y. F., Chu C. M., Huang M. J., Sheen I. S., Yang C. Y., Lin D. Y. Determinants for hepatitis B e antigen clearance in chronic type B hepatitis. Liver. 1984 Oct;4(5):301–306. doi: 10.1111/j.1600-0676.1984.tb00942.x. [DOI] [PubMed] [Google Scholar]
  15. Lok A. S., Novick D. M., Karayiannis P., Dunk A. A., Sherlock S., Thomas H. C. A randomized study of the effects of adenine arabinoside 5'-monophosphate (short or long courses) and lymphoblastoid interferon on hepatitis B virus replication. Hepatology. 1985 Nov-Dec;5(6):1132–1138. doi: 10.1002/hep.1840050612. [DOI] [PubMed] [Google Scholar]
  16. Nicholson J. K., McDougal J. S., Jaffe H. W., Spira T. J., Kennedy M. S., Jones B. M., Darrow W. W., Morgan M., Hubbard M. Exposure to human T-lymphotropic virus type III/lymphadenopathy-associated virus and immunologic abnormalities in asymptomatic homosexual men. Ann Intern Med. 1985 Jul;103(1):37–42. doi: 10.7326/0003-4819-103-1-37. [DOI] [PubMed] [Google Scholar]
  17. Noonan C. A., Yoffe B., Mansell P. W., Melnick J. L., Hollinger F. B. Extrachromosomal sequences of hepatitis B virus DNA in peripheral blood mononuclear cells of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5698–5702. doi: 10.1073/pnas.83.15.5698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Novick D. M., Brown D. J., Lok A. S., Lloyd J. C., Thomas H. C. Influence of sexual preference and chronic hepatitis B virus infection on T lymphocyte subsets, natural killer activity, and suppressor cell activity. J Hepatol. 1986;3(3):363–370. doi: 10.1016/s0168-8278(86)80490-1. [DOI] [PubMed] [Google Scholar]
  19. Novick D. M., Lok A. S., Thomas H. C. Diminished responsiveness of homosexual men to antiviral therapy for HBsAg-positive chronic liver disease. J Hepatol. 1985;1(1):29–35. doi: 10.1016/s0168-8278(85)80065-9. [DOI] [PubMed] [Google Scholar]
  20. Pahwa S. G., Quilop M. T., Lange M., Pahwa R. N., Grieco M. H. Defective B-lymphocyte function in homosexual men in relation to the acquired immunodeficiency syndrome. Ann Intern Med. 1984 Dec;101(6):757–763. doi: 10.7326/0003-4819-101-6-757. [DOI] [PubMed] [Google Scholar]
  21. Perrillo R. P., Campbell C. R., Sanders G. E., Regenstein F. G., Bodicky C. J. Spontaneous clearance and reactivation of hepatitis B virus infection among male homosexuals with chronic type B hepatitis. Ann Intern Med. 1984 Jan;100(1):43–46. doi: 10.7326/0003-4819-100-1-43. [DOI] [PubMed] [Google Scholar]
  22. Pinching A. J., Weber J. N., Rogers L. A., Berrie E. L., Jeffries D. J., Harris J. R. Longitudinal immunological studies on a cohort of initially symptom-free homosexual men in London with respect to HTLV-III serology. Adv Exp Med Biol. 1985;187:67–72. doi: 10.1007/978-1-4615-9430-7_6. [DOI] [PubMed] [Google Scholar]
  23. Poitrine A., Chousterman S., Chousterman M., Naveau S., Thang M. N., Chaput J. C. Lack of in vivo activation of the interferon system in HBsAg-positive chronic active hepatitis. Hepatology. 1985 Mar-Apr;5(2):171–174. doi: 10.1002/hep.1840050202. [DOI] [PubMed] [Google Scholar]
  24. Preble O. T., Rook A. H., Steis R., Silverman R. H., Krause D., Quinnan G. V., Masur H., Jacob J., Longo D., Gelmann E. P. Interferon-induced 2'-5' oligoadenylate synthetase during interferon-alpha therapy in homosexual men with Kaposi's sarcoma: marked deficiency in biochemical response to interferon in patients with acquired immunodeficiency syndrome. J Infect Dis. 1985 Sep;152(3):457–465. doi: 10.1093/infdis/152.3.457. [DOI] [PubMed] [Google Scholar]
  25. Sampliner R. E., Hamilton F. A., Iseri O. A., Tabor E., Boitnott J. The liver histology and frequency of clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers. Am J Med Sci. 1979 Jan-Feb;277(1):17–22. doi: 10.1097/00000441-197901000-00002. [DOI] [PubMed] [Google Scholar]
  26. Scullard G. H., Pollard R. B., Smith J. L., Sacks S. L., Gregory P. B., Robinson W. S., Merigan T. C. Antiviral treatment of chronic hepatitis B virus infection. I. Changes in viral markers with interferon combined with adenine arabinoside. J Infect Dis. 1981 Jun;143(6):772–783. doi: 10.1093/infdis/143.6.772. [DOI] [PubMed] [Google Scholar]
  27. Scully L. J., Shein R., Karayiannis P., McDonald J. A., Thomas H. C. Lymphoblastoid interferon therapy of chronic HBV infection. A comparison of 12 vs. 24 weeks of thrice weekly treatment. J Hepatol. 1987 Aug;5(1):51–58. doi: 10.1016/s0168-8278(87)80061-2. [DOI] [PubMed] [Google Scholar]
  28. Smith C. I., Weissberg J., Bernhardt L., Gregory P. B., Robinson W. S., Merigan T. C. Acute Dane particle suppression with recombinant leukocyte A interferon in chronic hepatitis B virus infection. J Infect Dis. 1983 Nov;148(5):907–913. doi: 10.1093/infdis/148.5.907. [DOI] [PubMed] [Google Scholar]
  29. Steis R. G., Smith J. W., 2nd, Urba W. J., Clark J. W., Itri L. M., Evans L. M., Schoenberger C., Longo D. L. Resistance to recombinant interferon alfa-2a in hairy-cell leukemia associated with neutralizing anti-interferon antibodies. N Engl J Med. 1988 Jun 2;318(22):1409–1413. doi: 10.1056/NEJM198806023182201. [DOI] [PubMed] [Google Scholar]
  30. Thomas H. C., Scully L. J. Antiviral therapy in hepatitis B infection. Br Med Bull. 1985 Oct;41(4):374–380. doi: 10.1093/oxfordjournals.bmb.a072079. [DOI] [PubMed] [Google Scholar]
  31. Vento S., Hegarty J. E., Alberti A., O'Brien C. J., Alexander G. J., Eddleston A. L., Williams R. T lymphocyte sensitization to HBcAg and T cell-mediated unresponsiveness to HBsAg in hepatitis B virus-related chronic liver disease. Hepatology. 1985 Mar-Apr;5(2):192–197. doi: 10.1002/hep.1840050206. [DOI] [PubMed] [Google Scholar]
  32. Viola L. A., Barrison I. G., Coleman J. C., Paradinas F. J., Fluker J. L., Evans B. A., Murray-Lyon I. M. Natural history of liver disease in chronic hepatitis B surface antigen carriers. Survey of 100 patients from Great Britain. Lancet. 1981 Nov 21;2(8256):1156–1159. doi: 10.1016/s0140-6736(81)90600-0. [DOI] [PubMed] [Google Scholar]
  33. Weller I. V., Fowler M. J., Monjardino J., Thomas H. C. The detection of HBV-DNA in serum by molecular hybridisation: a more sensitive method for the detection of complete HBV particles. J Med Virol. 1982;9(4):273–280. doi: 10.1002/jmv.1890090405. [DOI] [PubMed] [Google Scholar]
  34. Weller I. V., Lok A. S., Mindel A., Karayiannis P., Galpin S., Monjardino J., Sherlock S., Thomas H. C. Randomised controlled trial of adenine arabinoside 5'-monophosphate (ARA-AMP) in chronic hepatitis B virus infection. Gut. 1985 Jul;26(7):745–751. doi: 10.1136/gut.26.7.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. von Wussow P., Hartmann F., Freund M., Poliwoda H., Deicher H. Leucocyte-derived interferon-alpha in patients with antibodies to recombinant IFN-alpha 2b. Lancet. 1988 Apr 16;1(8590):882–883. doi: 10.1016/s0140-6736(88)91628-5. [DOI] [PubMed] [Google Scholar]

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